Schering-Plough Research Institute, Newhouse, Lanarkshire, UK.
Psychopharmacology (Berl). 2009 Nov;206(4):699-714. doi: 10.1007/s00213-009-1570-z. Epub 2009 May 22.
Asenapine, a novel psychopharmacologic agent in the development for schizophrenia and bipolar disorder, has high affinity for serotonergic, alpha-adrenergic, and dopaminergic receptors, suggesting potential for antipsychotic and cognitive-enhancing properties.
The effects of asenapine in rat models of antipsychotic efficacy and cognition were examined and compared with those of olanzapine and risperidone.
Amphetamine-stimulated locomotor activity (Amp-LMA; 1.0 or 3.0 mg/kg s.c.) and apomorphine-disrupted prepulse inhibition (Apo-PPI; 0.5 mg/kg s.c.) were used as tests for antipsychotic activity. Delayed non-match to place (DNMTP) and five-choice serial reaction (5-CSR) tasks were used to assess short-term spatial memory and attention, respectively. Asenapine doses varied across tasks: Amp-LMA (0.01-0.3 mg/kg s.c.), Apo-PPI (0.001-0.3 mg/kg s.c.), DNMTP (0.01-0.1 mg/kg s.c.), and 5-CSR (0.003-0.3 mg/kg s.c.).
Asenapine was highly potent (active at 0.03 mg/kg) in the Amp-LMA and Apo-PPI assays. DNMTP or 5-CSR performance was not improved by asenapine, olanzapine, or risperidone. All agents (P < 0.01) reduced DNMTP accuracy at short delays; post hoc analyses revealed that only 0.1 mg/kg asenapine and 0.3 mg/kg risperidone differed from vehicle. All active agents (asenapine, 0.3 mg/kg; olanzapine, 0.03-0.3 mg/kg; and risperidone, 0.01-0.1 mg/kg) significantly impaired 5-CSR accuracy (P < 0.05).
Asenapine has potent antidopaminergic properties that are predictive of antipsychotic efficacy. Asenapine, like risperidone and olanzapine, did not improve cognition in normal rats. Rather, at doses greater than those required for antipsychotic activity, asenapine impaired cognitive performance due to disturbance of motor function, an effect also observed with olanzapine and risperidone.
阿塞那平是一种新型精神药理学药物，用于治疗精神分裂症和双相情感障碍，对 5-羟色胺能、α-肾上腺素能和多巴胺能受体具有高亲和力，这表明它具有抗精神病和认知增强的特性。
研究阿塞那平在抗精神病疗效和认知的大鼠模型中的作用，并与奥氮平利培酮进行比较。
采用安非他命刺激的运动活动（Amp-LMA；1.0 或 3.0mg/kg sc）和阿扑吗啡破坏的预备脉冲抑制（Apo-PPI；0.5mg/kg sc）作为抗精神病活性的测试。延迟非匹配到位置（DNMTP）和五选择连续反应（5-CSR）任务分别用于评估短期空间记忆和注意力。阿塞那平的剂量在不同任务中有所不同：Amp-LMA（0.01-0.3mg/kg sc）、Apo-PPI（0.001-0.3mg/kg sc）、DNMTP（0.01-0.1mg/kg sc）和 5-CSR（0.003-0.3mg/kg sc）。
阿塞那平在 Amp-LMA 和 Apo-PPI 测定中具有高活性（0.03mg/kg 时有效）。DNMTP 或 5-CSR 表现未被阿塞那平、奥氮平或利培酮改善。所有药物（P<0.01）均降低了短延迟时的 DNMTP 准确性；事后分析显示，只有 0.1mg/kg 阿塞那平和 0.3mg/kg 利培酮与载体不同。所有活性药物（阿塞那平，0.3mg/kg；奥氮平，0.03-0.3mg/kg；利培酮，0.01-0.1mg/kg）均显著降低 5-CSR 准确性（P<0.05）。
阿塞那平具有有效的抗多巴胺能特性，可预测抗精神病疗效。阿塞那平与利培酮和奥氮平一样，未改善正常大鼠的认知。相反，在大于抗精神病活性所需的剂量下，阿塞那平由于运动功能障碍而损害认知表现，这种作用也在奥氮平和利培酮中观察到。
